The Eagles confirmed Sheppard's decision on Tuesday, with the veteran backman having taken the advice of medical specialists following the impacts of recent head knocks.
Sheppard hangs up the boots after 216 games in the blue and gold, having joined the club via the 2009 National Draft at Pick 7.
The 30-year-old soon emerged as a key pillar in Adam Simpson's backline, featuring in the club's 2015 Grand Final loss to the Hawks as a reliable lockdown option in defence.
Sheppard claimed his maiden All-Australian selection last year following a stellar campaign with the Eagles, where he averaged 15.89 disposals, 3.44 rebounds 50s and 6.22 marks per game in reduced quarter durations.
After considering his future and wellbeing, Sheppard decided to announce his retirement this week, ending a cherished career with West Coast.
Sheppard joins young forward Daniel Venables in also having to abruptly end his AFL career after battling ongoing concussion setbacks.